Novel tau filament fold in corticobasal degeneration
Zhang W, Tarutani A, Newell KL, Murzin AG, Matsubara T, Falcon B, Vidal R, Garringer HJ et al.. Nature, 2020-02-12
Topic: Disease mechanisms in lab and animal studies
Plain-language summary
Corticobasal degeneration (CBD) is a neurodegenerative tauopathy-a class of disorders in which the tau protein forms insoluble inclusions in the brain-that is characterized by motor and cognitive disturbances 1-3 . The H1 haplotype of MAPT (the tau gene) is present in cases of CBD at a higher frequency than in controls 4,5 , and genome-wide association studies have identified additional risk factors 6 . By histology, astrocytic plaques are diagnostic of CBD 7,8 ; by SDS-PAGE, so too are detergent-insoluble, 37 kDa fragments of tau 9 . Like progressive supranuclear palsy, globular glial tauopathy and argyrophilic grain disease 10 , CBD is characterized by abundant filamentous tau inclusions that are made of isoforms with four microtubule-binding repeats 11-15 . This distinguishes such '4R' tauopathies from Pick's disease (the filaments of which are made of three-repeat (3R) tau isoforms) and from Alzheimer's disease and chronic traumatic encephalopathy (CTE) (in which both 3R and 4R isoforms are found in the filaments) 16 . Here we use cryo-electron microscopy to analyse the structures of tau filaments extracted from the brains of three individuals with CBD. These filaments were identical between cases, but distinct from those seen in Alzheimer's disease, Pick's disease and CTE 17-19 . The core of a CBD filament comprises residues lysine 274 to glutamate 380 of tau, spanning the last residue of the R1 repeat, the whole of the R2, R3 and R4 repeats, and 12 amino acids after R4. The core adopts a previously unseen four-layered fold, which encloses a large nonproteinaceous density. This density is surrounded by the side chains of lysine residues 290 and 294 from R2 and lysine 370 from the sequence after R4.
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APA 7th
Zhang, W., Tarutani, A., Newell, K. L., Murzin, A. G., Matsubara, T., Falcon, B., et al. (2020). Novel tau filament fold in corticobasal degeneration. Nature. https://doi.org/10.1038/s41586-020-2043-0
Vancouver
Zhang W, Tarutani A, Newell KL, Murzin AG, Matsubara T, Falcon B, et al. Novel tau filament fold in corticobasal degeneration. Nature. 2020. doi:10.1038/s41586-020-2043-0. PMID: 32050258.
BibTeX
@article{zhang2020-32050258,
author = {Zhang, W. and Tarutani, A. and Newell, K. L. and Murzin, A. G. and Matsubara, T. and Falcon, B. and Vidal, R. and Garringer, H. J. and others},
title = {{Novel tau filament fold in corticobasal degeneration}},
journal = {Nature},
year = {2020},
doi = {10.1038/s41586-020-2043-0},
pmid = {32050258},
url = {https://doi.org/10.1038/s41586-020-2043-0}
}
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Key findings
- Here we use cryo-electron microscopy to analyse the structures of tau filaments extracted from the brains of three individuals with CBD.
- These filaments were identical between cases, but distinct from those seen in Alzheimer's disease, Pick's disease and CTE 17-19 .
- The core of a CBD filament comprises residues lysine 274 to glutamate 380 of tau, spanning the last residue of the R1 repeat, the whole of the R2, R3 and R4 repeats, and 12 amino acids after R4.
- The core adopts a previously unseen four-layered fold, which encloses a large nonproteinaceous density.
- This density is surrounded by the side chains of lysine residues 290 and 294 from R2 and lysine 370 from the sequence after R4.
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Study details
- Evidence strengthLow
How this study scored 52/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 30 of the 58 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32050258) |
| Free to read | 2 / 2 | Free to read |
| Points | 30 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 30 of the 58 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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